Expressions of Transcriptional Factors SOX2, Oct4, Nanog in Experimental Varicocele; Correlation with P21 Expression In Stages IX-XII Of Spermatogenesis

Background: The varicocele (VCL) has been reported to pathologically affect the spermatogenesis. The SOX2, as main pularipotency/self renewal regulator of SSCs, inassociation with Oct4, as target gene of SOX2, results in Sox-2-Oct4 complex, which in turn triggers the SSCs self-renwal. The Nanog has been reported to express in SSCs during stage XII of spermatogenesis, resulting in SSCs subpoulation self-renewal. Moreover, the p21, as cyclin dependent kinase inhibitor, has been known as a negative regulator of SSCs proliferation. Thus, the present study was performed to analyze the cross-link between transcriptional factors SOX2, Oct4 and Nanog with p21 during stagesIX-XII of spermatogenesis in experimentallyinduced VCL versus control animals. Methods: For his purpose, 18 mature Wistar rats were randomly divided into control-sham, 2months and 4 months VCL-induced groups. Simple laparotomy was performed in controlsham group. Following test termination, the mRNA levels of SOX2, Oct4, Nanog and p21 were evaluated using RT-PCR. By using IHC staining, the SOX2+, Oct4+, and p21+ cells were traced in seminiferous tubules in stages of IX-XII. Results: The animals in VCL-induced groups, represented diminished expression of Nanog, enhanced mRNA levels of SOX2, Oct4 and p21 versus control-sham animals. Moreover, the numbers of SOX2+, Oct4+, p21+ and Nanog+ cells per seminiferous tubules (stages IX-XII) were increased and decreased, respectively. Conclusion: The overexpression of p21 negatively regulates the Nanog and its promoter SOX2-Oct4 complex genetic cross-link, which ultimately results in SSCs self-renewal suppression in VCL condition.

Keywords:

Varicocele , Self-renewal SOX2 , Oct4 , Nanog , p21